Unipharm Challenges Validity of Patent Term Extension for Neurim’s Circadin in Israel

Unipharm has challenged the validity of the patent term extension obtained by Neurim for Israel Patent 103411 for a drug for sleep disorder based on melatonin and marketed as Circadin.

BACKGROUND
Neurim has developed a drug for sleep disorder called Circadin. The drug is based on melatonin, and in the UK, a patent term extension was refused since the active ingredient is used in a drug called Regulin that is used to get sheep to enter the mating season a month early.

Anyway, the UK Patent Office decision was appealed through the UK courts, and eventually the Rt Hon Sir Robin Jacob referred the issue to the European Court of Justice, since although Circadin wasn’t the first approved use of the active agreement, insomnia in humans and tupping in sheep are not exactly the same, and the intention of the law was to provide compensation for the long time it takes to get regulatory approval.

In Israel, the Law allows patent term extensions for the shortest period granted by a Bolar country that grants extensions, so the Israel Patent Office refused to grant an extension.

However, the ECJ then overturned the UK ruling and allowed a patent term extension, so the Israel Patent Office decision was appealed to the District Court.

The 20 year period (sans extension) lasted until 11 October 2012, and after Judge Ben-Zion Greenberger of the Jerusalem District Court ruled that an extension was in order, Adv. Assa Kling, the Commissioner of Patents awarded a temporary extension of six months until 11 April 2013.

The original application for an extension in Israel was filed three months late, but the previous Commissioner of Patents retroactively allowed the application to be considered.

Unipharm opposed the patent term extension on three legal points:

Equitable behaviour of the Applicant and whether the extension was legal

Whether the patent in question was to be considered the “basic patent” under Section 64a of the Israel Law

Whether Circadin was the first drug containing the active ingredient as required by 64d of the Israel Law

THE ISSUE OF (IN)EQUITABLE BEHAVIOUR

The request for a patent term extension is conducted by the applicant in an ex partes procedure, and so Unipharm argued that a high standard of equitable behaviour was required and alleged that Neurim had withheld or suppressed relevant information. The Commissioner of Patents accepted that the Law required equitable behavior and had no problem with Unipharm challenging on these grounds, but found the claim of inequitable behaviour to invalidate the patent term extension was not sufficiently substantiated to invalidate the patent term extension.

The first issue raised was that the request for a patent term extension was filed late, and Section 164 -1a of the Law only allows extensions in cases where neither the applicant nor his representative had control and where the delay could not be prevented. Dr Kling was not convinced that the relevant facts were withheld from his predecessor and so saw no reason to retroactively cancel the extension provided.

Regarding Regulin, the Applicant’s position was that the fact that Regulin had previously received marketing permission and registration in the list of pharmaceuticals was irrelevant since it wasn’t “for medical use” as required for a previous registration by Section 64D(3) of the Law. Furthermore, the Applicant considered that the District Court’s ruling supported this interpretation and rendered the issue moot. On this issue, Commissioner Kling considered that Regulin should have been discussed at the first opportunity, but had, nevertheless, been fully considered in earlier hearings and so could not be considered inequitable behavior as far as patent term extensions are to be considered.

Another issue raised was the availability of Melatonin as a non-regulated food supplement for treating sleep dissorders. Here Neurim’s position was that the Law requires first regulatory approval and does not relate to unregulated preparations that may be available. Here Dr Kling was unconvinced that Neurim was obliged to report melatonin that was available as a food stuff.

A melatonin containing preparation called Prime-x was available in the US, and was not reported. Here, Commissioner Kling ruled that the requirement to report this was similar to that concerning Regulin.

Regarding the issue concerning Regulin in the UK; here Neurim apparently failed to inform the IPO that the patent term extension was refused due to the earlier registration of Regulin. Neurim claimed to be unaware of the requirement to inform the Israel Patent Office regarding developments in the UK, claiming that they believed these to be irrelevant. The Israel Counsel handling the patent term extension was not representing Neurim in Europe, and wasn’t in the loop. Here Commissioner Kling was critical that the full picture wasn’t provided, but felt that this was insufficient proof of equitable behavior to invalidate the request for patent term extension.

Regarding developments in the US – in August and October 2011, the Israel Patent Office asked whether the applicant had requested a patent term extension in the US, and was informed that none had been requested. The Opposer considered that Neurim had witheld information in this regard. It transpires that a request for an investigational New Drug (IND) had been filed, but no request for a New Drug Application (NDA) had been filed.

Adv. Kling considered that the statements and explanations were sufficient to overcome arguments that there was sufficiently inequitable behaviour to warrant the patent term extension being cancelled, but emphasized that the applicant for a patent term extension is required to document all these issues in a timely manner.

IS THE PATENT “THE BASIC PATENT” AS REQUIRED BY THE LAW

The Opposer claimed that the Circadin patent in question was not a “basic patent” in that it claimed a new use for a known active ingredient, and that the legislators never intended to grant patent term extensions in Israel for such patents, but only for those with new active ingredients. Neurim claimed that the 103411 patent is for controlled release of melatonin and considered this a “basic patent”. The requirement of “basic patent” is not necessarily synonymous with first patent. Furthermore, Neurim’s position was that most ground-breaking pharmaceutical patents were tied to uses, and not merely to active ingredients.

Since Section 64a defines the basic patent as a patent that protects a material, manufacturing process, use of material or a medical formulation that includes… Commissioner Kling rejected the Opposer’s interpretation. Furthermore, he ruled that the 103411 patent wasn’t a use patent per se, but rather a novel formulation that was used for a specific purpose.

It seems that the issue here was whether a Swiss type claim formulation made the subject matter a secondary use. Dr Kling wasn’t convinced, and didn’t believe that Dr Tomer of Unipharm was really convinced either.

In summary, Dr Kling ruled that the 103411 patent could be considered a basic patent in accordance with the Law.

WAS CIRCADIN THE FIRST PATENT CONTAINING THE ACTIVE INGREDIENT TO OBTAIN REGULATORY APPROVAL?

Adv. Kling considered that the District Court’s ruling did not prevent him from analyzing this question directly. Professor Zisapel’s interpretation of the term “first medical approval” was to exclude non-regulated usage on one hand, and regulated usage for animals on the other hand. Dr Tomer of Unipharm followed the argument of the British Patent Office, and noted that there is one register. There was an interesting discussion concerning a treatment for head lice, that incapacitated lice and so had a physiological effect on lower animals, but was used to treat humans infected with lice. Adv. Kling adopted the interpretation of the ECJ and ruled that since the registration for causing sheep to breed earlier was of no help in receiving a patent of regulatory approval for Circadin for treating insomnia, the narrow interpretation was inappropriate.

CONCLUSION

The Opposition was rejected and a patent term extension until 22 April 2017 was granted.

COMMENTS

Circadin is a very rare instance of an Israeli drug brought to market from first development through trials and regulatory approval.

I have been following this case with interest, as my former partner, the late Dr Stanley Davis wrote the original application.

I am probably unable to comment substantively on the ruling due to attorney client privilege, and I think we should let sleeping sheep lie…